About this Research Topic
Many human pathogens have evolved strategies to evade host immune responses, reducing the efficacy of currently available antibiotics and contributing to ongoing tissue inflammation. Due to a limited number of new drugs in the antibiotic discovery pipeline, recent attention has focused on the repurposing of existing agents as a strategy for accelerating their potential use in the clinical setting. One emerging area of research is the development of therapeutics targeting host factors involved in the response to infection, with the goal of increasing the effectiveness of currently available antibiotic regimens and reducing the emergence of antibiotic resistance. An important advantage of such host-directed therapies is the possibility of exploiting pharmaceutical advances in areas of intense research, including cancer or metabolic and cardiovascular diseases. This Research Topic will focus specifically on potential anti-infective therapies targeting the metabolism of innate immune cells.
Multiple themes at the crossroad of metabolism and immunity are at the forefront of immunological research in infectious diseases. They include the effects of various signals, such as growth hormones, nutrient availability, and cytokines, among others, on differentiation and activation of innate – myeloid and lymphoid – cells. For example, much is known of the cellular pathways linking glucose metabolism and immunity in various immune cell types. However, much remains to be understood of which mechanisms differentiate innate lymphoid from myeloid cells or cell subsets (e.g., different subsets of innate lymphoid cells) from each other. Moreover, questions still remain on the metabolic responses of the same cell type when exposed to the different cytokine environments characteristic of different infectious pathologies. In this Frontiers in Microbiology Research Topic, we anticipate that emphasis will be placed on myeloid cells. Ample literature now exists on the connections between metabolism and function of macrophages and dendritic cells, on the link between inflammatory signaling (e.g., TNFα) and systemic metabolism (e.g., insulin resistance), and vice versa, or on the metabolic underpinnings of trained immunity. Moreover, of great importance to our ability to perform research leading to improvement of human health is the understanding of how responses of murine cells mimic the human situation, and how mouse genetic background (or microbiota) may affect the mechanisms investigated.
We are confident that an overview of diverse themes within the context of the intersection of metabolism and immunity in innate immune cells will reinforce the growing belief that manipulation of immunometabolic pathways may serve as a novel host-directed approach to controlling certain infections. For example, activation of AMP-activated protein kinase (AMPK) with the anti-diabetic drug metformin was reported to reduce M. tuberculosis burden and immunopathology in mice, presumably due to induction of autophagy and oxidative phosphorylation. Similarly, pharmacological inhibition of mammalian target of rapamycin complex 1 (mTORC1) or upregulation of autophagy-related proteins by small molecules lead to enhanced macrophage clearance of intracellular organisms, including Salmonella, Francisella, and Mycobacteria. We expect that this Research Topic will provide a comprehensive overview of the literature and attract original research on existing modulators of immunometabolic pathways in innate immune cells, and their potential applicability as novel treatment strategies in the context of infectious diseases.
Keywords: Host-Directed Therapy, Innate Immunity, Metabolism, Persistence, Inflammation
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